Effects of the Ketogenic Diet on Pentylenetetrazole-Induced Seizure

Kim, Dong Wook; Kim, Hee Seok; Ko, Tae Sung; Chae, Soo Ahn; Kim, Ki Joong; Hwang, Yong Seung

Abstract

PURPOSE: Despite decades of clinical experience with the ketogenic diet(KD), its efficacy and mechanisms of action have been examined in few animal studies. The present study was designed to investigate the effects of the KD on pentylenetetrazole(PTZ)-induced seizure severity in rats.
METHODS
Thirty-eight male Sprague-Dawley rats were divided into two equal groups. Dietary treatment was initiated at P22. The KD group was fasted for a day and then fed a KD consisting of a [fat] : [protein+carbohydrate] ratio of 4.3 : 1 for 26 days, while the control group was fed a standard rodent chow. Blood beta-hydroxybutyrate(beta-OHB) levels were assayed on treatment days 0, 20, and 24. Seizures were chemically induced by intraperitoneal injection of PTZ(60mg/kg of body weight) between treatment days 22 and 27. Seizure severity was evaluated by using a scoring system of seizure behaviors : 0, no seizure; 0.5, abnormal behavior; 1, myoclonic jerk; 2, myoclonic jerk with jumping; 3, forelimb clonus with preserving righting reflex; 4, generalized clonic seizure with brief loss of righting reflex; 5, generalized tonic clonic seizure; 6, expire. A greater score represents a more severe seizure.
RESULTS
Blood levels of beta-OHB were low(<0.3mM) and showed no significant differences in both groups on day 0. Rats fed the KD developed an increased level of ketosis that was significantly above the levels found in the control group on days 20 and 24 (p<0.001). The KD group(2.37+/-0.27) exhibited significantly(p<0.05) lower seizure score than the control group(3.37+/-0.35).
CONCLUSION
The KD was previously reported to increase PTZ-induced seizure thresholds in rats. In our study, rats fed the KD exhibited significantly decreased PTZ-induced seizure scores relative to controls. This suggests that the KD can not only increase the resistance to seizure but also decrease the severity of seizure induced by PTZ.